Neoplasia of the Testis - Retroperitoneal …...Neoplasia of the Testis - Retroperitoneal Lymphadenectomy Histopathology Reporting Guide Not provided SIZE OF LARGEST NODAL METASTASIS

Neoplasia of the Testis - Retroperitoneal Lymphadenectomy Histopathology Reporting Guide

Not provided SIZE OF LARGEST NODAL METASTASIS (select all that apply) (Note 4)

PRE-PROCEDURE SERUM TUMOUR MARKERS(select all that apply) (Note 2)

Not provided

SPECIMEN(S) SUBMITTED (select all that apply) (Note 3)Not specified

Brain Liver Lung Other, specify

Cannot be assessed Maximum dimension

Additional dimensions

X

........ mm

MARGIN STATUS (Note 7)Cannot be assessedNot involved

Closest margin Distance of tumour from closest margin Involved, specify

mm

Specify serum tumour markers used, level and date markers were drawn

Date AFP

LDH IU/L b-HcG

....... mm

....... mm

Version 1.0 Published August 2017 ISBN: 978-1-925687-08-8 Page 1 of 2

Family/Last name

Given name(s)

Patient identifiers Date of request Accession/Laboratory number

Elements in black text are REQUIRED. Elements in grey text are RECOMMENDED.

Date of birth DD – MM – YYYY

CLINICAL INFORMATION (Note 1)

Previous therapy, specify

Previous history of testicular cancer, specify

Other, specify

BLOCK IDENTIFICATION KEY (Note 5)(List overleaf or separately with an indication of the nature and origin of all tissue blocks)

Germ cell tumour, specify type and percentageProvided

Retroperitoneal lymphadenectomy, specify nodal site

%

%

%

%

Viable tumour Present Absent

%

Other, specify

Serum tumour markers within normal limits OR

ug/L

IU/L IU/L

HISTOLOGICAL TUMOUR TYPE (Note 6) (Value list from the World Health Organisation Classification of tumours. Pathology and genetics of urinary system and male genital organs (2016))

No disease Necrosis Viable tumour




DD – MM – YYYY

Regional lymph nodes (pN) NX Regional lymph nodes cannot be assessedN0 No regional lymph node metastasisN1 Metastasis with a lymph node mass 2 cm or smaller

in greatest dimension and less than or equal to five nodes positive, none larger than 2 cm in greatest dimension

N2 Metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension; or more than five nodes positive, none larger than 5 cm; or evidence of extranodal extension of tumour

N3 Metastasis with a lymph node mass larger than 5 cm in greatest dimension

PATHOLOGIC STAGING (TNM 8th edition)## ^(Note 9)

No distant metastasesM1 Distant metastasis M1a Non-retroperitoneal nodal or pulmonary metastases M1b Non-pulmonary visceral metastases

Distant metastasis (pM) (if resected)

## Used with the permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2016) published by Springer Science+Business Media.

^ Please note that implementation of AJCC TNM 8th edition has been deferred until January 2018 in some jurisdictions. UICC 7th edition or AJCC 7th edition may be useful in the interim.

Version 1.0 Published August 2017 ISBN: 978-1-925687-08-8 Page 2 of 2

EXTRANODAL EXTENSION (Note 8)

Not identified Present Indeterminate

1

Scope

The dataset has been developed for the reporting of retroperitoneal and other lymphadenectomy

specimens as well as visceral metastasis excision specimens from patients with malignant tumours of

the testis. The protocol applies to all malignant germ cell and sex cord-stromal tumours of the testis.

Paratesticular malignancies are excluded.

Note 1 - Clinical information (Recommended)

Reason/Evidentiary Support

Retroperitoneal lymphadenectomies (RPLNDs) may be performed at the time of diagnosis of a

testicular tumour, or may be performed after chemotherapy, and this will affect the likely

pathological changes seen. Although the majority of excisions will be for germ cell tumours, primary

prophylactic excisions for malignant sex cord- stromal tumours are also occasionally performed.1

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Note 2 - Pre-procedure serum tumour markers (Recommended)


Serum marker studies play a key role in the clinical management of patients with testicular germ cell

tumours and in the monitoring of recurrent disease.2-4 Most patients who undergo post

chemotherapy RPLND will have negative markers following orchiectomy as those with positive

markers will be treated with further chemotherapy or radiotherapy. The occurrence of elevated

serum levels of alpha-fetoprotein (AFP) or the beta subunit of human chorionic gonadotropin (b-

hCG) may indicate the need for additional sections of certain specimens if the initial findings do not

account for such elevations.

2

Anatomic Stage/Prognostic Groups

Group T N M S

Stage 0 pTis N0 M0 S0

Stage I pT1-4 N0 M0 SX

Stage IA pT1 N0 M0 S0

Stage IB pT2 N0 M0 S0

pT3 N0 M0 S0

pT4 N0 M0 S0

Stage IS Any pT/TX N0 M0 S1-3

Stage II Any pT/TX N1,N2,N3 M0 SX

Stage IIA Any pT/TX N1 M0 S0

Any pT/TX N1 M0 S1

Stage IIB Any pT/TX N2 M0 S0

Any pT/TX N2 M0 S1

Stage IIC Any pT/TX N3 M0 S0

Any pT/TX N3 M0 S1

Stage III Any pT/TX Any N M1 SX

Stage IIIA Any pT/TX Any N M1a S0

Any pT/TX Any N M1a S1

Stage IIIB Any pT/TX N1,N2,N3 M0 S2


Stage IIIC Any pT/TX N1,N2,N3 M0 S3


Any pT/TX Any N M1b Any S

A “y” prefix indicates those cases in which classification is performed during or following initial

multimodality therapy (i.e., chemotherapy, radiation therapy, or both chemotherapy and radiation

therapy).

Prognostic Factors

Serum Tumour Markers (S)

SX Serum marker studies not available or performed

S0 Serum marker study levels within normal limits

LDH hCG (mIU/mL) AFP (ng/mL)

S1 <1.5 x N# and <5,000 and <1,000

S2 1.5-10 x N or 5,000-50,000 or 1,000-10,000

S3 >10 x N or >50,000 or >10,000

# N indicates the upper limit of normal for the LDH assay.

The Serum Tumour Markers (S) category comprises the following:

AFP – half-life 5 to 7 days

hCG – half-life 1 to 3 days

Lactate dehydrogenase (LDH)

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3

Note 3 - Specimens submitted (Required)


The type of retroperitoneal surgery performed is dependent on which testis was affected by tumour

and a number of different surgical approaches are possible. Although there are exceptions, right-

sided tumours metastasize to the interaortocaval lymph nodes first followed by the precaval and

paracaval lymph nodes. Left-sided testicular tumours metastasize to the para- and preaortic areas.

Contralateral involvement is more frequent in right-sided tumours as well as in bulky disease. The

practice of specimen submission differs greatly, but often surgeons will resect separate nodal sites in

separate containers.

After chemotherapy, it is common practice to excise other remaining sites of disease, apart from

RPLNDs and these should be identified.

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Note 4 - Size of largest nodal metastasis (Required)


A number of studies have shown that the size of the retroperitoneal nodes is associated with the

presence of tumour (teratoma and also of viable malignant elements). Nodal size may be difficult to

measure when nodes are confluent. We suggest that where separate nodes are not readily

identifiable then the largest diameter of the overall tumour be taken on macroscopy.5,6 The other

two dimensions are recommended.

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Note 5 - Block identification key (Recommended)


The origin/designation of all tissue blocks should be recorded and it is preferable to document this

information in the final pathology report. This is particularly important should the need for internal

or external review arise. The reviewer needs to be clear about the origin of each block in order to

provide an informed specialist opinion. If this information is not included in the final pathology

report, it should be available on the laboratory computer system and relayed to the reviewing

pathologist.

Recording the origin/designation of tissue blocks also facilitates retrieval of blocks, for example for

further immunohistochemical or molecular analysis, research studies or clinical trials.

4

Comprehensive sampling is essential for residual masses, as the identification of even a small area of

a different subtype can alter patient management and impact on prognosis. Although the

recommendation of one block per centimetre of tumour is usual, more may be required to

adequately represent all the macroscopically different areas of tumour. The number of nodes

harvested has been shown to impact on prognosis.7,8

Blocks are selected to represent:

all areas of the positive node(s) with different macroscopic appearances (solid, cystic,

pale or haemorrhagic)

the minimum distance of the tumour to the nearest resection margin (which may be

inked)

all macroscopically negative nodes to search for micrometastatic disease

total number of nodes resected.

It is recommended that a record is kept of a good representative paraffin block of tumour and if

frozen tissue is stored.

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Note 6 - Histological tumour type (Required)


In concordance with the dataset for Orchidectomy specimens, the World Health Organisation (WHO)

2016 classification of testicular tumours should be used.9

RPLND before treatment

The type of tumour identified in an RPLND is crucial information to determine further treatment.

The tumour in prechemotherapy RPLNDs (also referred to as primary RPLNDs) generally (but not

always) show similar findings to that in the orchidectomy specimen. In primary setting, pathologic N

staging is more commonly used to determine the need for adjuvant chemotherapy with pN0 and

pN1 leading to surveillance and pN2 and pN3 (rare) leading to adjuvant chemotherapy.

RPLND after treatment

After chemotherapy, and especially in late relapses, the pathology may be substantially different

from that seen in primary RPLND.10 In general terms, after chemotherapy, 40-50% of germ cell

tumour cases show pure necrosis with no viable tissue seen. A further 40% show teratoma, while the

remaining 10% show a mixture of ‘malignant’ germ cell elements such as embryonal carcinoma, or

yolk sac tumour, and a small number may show somatic transformation. Pure teratomatous

metastasis is generally treated by surgical excision alone, whereas patients who have other residual

germ cell tumour components are usually treated with additional chemotherapy. Metastatic sex

cord-stromal tumours are also occasionally operated upon.1 Even the type of tumour seen

substantially affects the prognostic and therapeutic implications11 with, for example, certain variants

5

being associated with a good outcome12 while others are associated with an intermediate13 or more

aggressive course.14 Diagnosis of these variants may be challenging and require expert consultation.

The percentage of ‘viable malignant cells’ has also shown to be a determinant of prognosis in a

number of studies.15-18 10% is the most common cut-off used to determine the need for further

treatment.

For post-chemotherapy residual masses, particularly in the absence of a biopsy diagnosis prior to

treatment, it is often useful to examine areas of necrosis, as ghost outlines of the tumour often

remain and allow the distinction between seminoma and non-seminomatous germ cell tumour. The

reporting of number and location of lymph nodes involved by necrosis, fibrosis, xanthomatous and

fibroxanthomatous reaction is important to the treating physician to evaluate the extent and

distribution of tumour in different lymph nodes. There is evidence that fibrosis often represents

neoplastic stroma originating from teratoma or yolk sac tumor. The spindle cells in the areas of

fibrosis are often reactive to cytokeratin and display allelic loss (85%) and 12p anomalies (33%)

characteristic of germ cell tumours. Xanthomatous and fibroxanthomatous reaction may sometimes

pose a diagnostic challenge and immunohistochemical staining for evaluation of residual tumour is

deemed necessary in occasional cases. It is important to recognise that residual viable malignancy

(embryonal carcinoma, yolk sac tumour, classical seminoma or choriocarcinoma) may trigger further

chemotherapy and therefore it is important to only report viable elements along with percentage of

viable tumour and not semi-viable or non-viable tumour. Necrosis and post-chemotherapy teratoma

would not usually trigger further therapy, unless the clinical situation dictates otherwise. In the case

of cystic trophoblastic tumour (CTT), an explanatory note should be provided to caution the

physicians against further chemotherapy. Data for CTT are limited but the largest study of 15

patients with follow-up showed that 11 did not recur, three showed late recurrences of possibly

unrelated yolk sac tumour and the one patient who did recur with a rise in hCG had unresected

residual masses.12 For post-chemotherapy RPLND, it may be desirable to embed more of the

specimen if it is found to contain necrosis or non-viable tumour to exclude small foci of viable

tumour.

Secondary somatic malignancy is rare and challenging to diagnose. The tumour typically consists of a

pure population of atypical mesenchymal or epithelial cells and occupies at least one low-power

field (×4 objective, 5 mm in diameter).9 Sarcomas are the most common type, though some post-

chemotherapy sarcoma-like tumours may be sarcomatoid yolk sac tumours.19 Primitive

neuroectodermal tumour (PNET) is another relatively common somatic-type malignancy which

behaves aggressively.20,21 Most carcinomas are adenocarcinomas, usually Not Otherwise Specified

(NOS) type. Occasionally, patients may develop nephroblastoma.22

A somatic malignancy in a metastasis increases likelihood of dying from the disease and if it is

localized, surgical resection is the optimal treatment.14 Patients usually respond poorly to the

treatment for conventional germ cell malignancy.23 Some somatic malignancies may respond to a

specific chemotherapy that is effective for the specific subtype, so accurate subtyping of the somatic

transformation is important.

6

WHO classification of tumours of the testis and paratesticular tissuea9

Descriptor ICD-O

codes

Germ cell tumours derived from germ cell neoplasia in situ (GCNIS)

Non-invasive germ cell neoplasia

Germ cell neoplasia in situ 9064/2

Specific forms of intratubular germ cell neoplasia

Tumours of one histological type (pure tumours)

Seminoma 9061/3

Seminoma with syncytiotrophoblast cells

Non-seminomatous germ cell tumours

Embryonal carcinoma 9070/3

Yolk sac tumour, postpubertal-type 9071/3

Trophoblastic tumours

Choriocarcinoma 9100/3

Non-choriocarcinomatous trophoblastic tumours

Placental site trophoblastic tumour 9104/3

Epithelioid trophoblastic tumour 9105/3

Cystic trophoblastic tumour

Teratoma, postpubertal-type 9080/3

Teratoma with somatic-type malignancies 9084/3

Non-seminomatous germ cell tumours of more than one histological type

Mixed germ cell tumours 9085/3

Germ cell tumours of unknown type

Regressed germ cell tumours 9080/1

Germ cell tumours unrelated to germ cell neoplasia in situ

Spermatocytic tumour 9063/3

Teratoma, prepubertal type 9084/0

Dermoid cyst

Epidermoid cyst

Well-differentiated neuroendocrine tumour (monodermal teratoma) 8240/3

Mixed teratoma and yolk sac tumour, prepubertal-type 9085/3

Yolk sac tumour, prepubertal-type 9071/3

Sex cord-stromal tumours

Pure tumours

Leydig cell tumour 8650/1

Malignant Leydig cell tumour 8650/3

Sertoli cell tumour 8640/1

Malignant Sertoli cell tumour 8640/3

Large cell calcifying Sertoli cell tumour 8642/1

Intratubular large cell hyalinizing Sertoli cell tumour 8643/1

Granulosa cell tumour

Adult granulosa cell tumour 8620/1

Juvenile granulosa cell tumour 8622/0

Tumours in the fibroma-thecoma group 8600/0

Mixed and unclassified sex cord-stromal tumours

7

Descriptor ICD-O

codes

Mixed sex cord-stromal tumour 8592/1

Unclassified sex cord-stromal tumour 8591/1

Tumour containing both germ cell and sex cord-stromal elements

Gonadoblastoma 9073/1

a The morphology codes are from the International Classification of Diseases for Oncology (ICD-O). Behaviour is coded /0 for benign tumours; /1 for unspecified, borderline, or uncertain behaviour; /2 for carcinoma in situ and grade III intraepithelial neoplasia; and /3 for malignant tumours.

© WHO/International Agency for Research on Cancer (IARC). Reproduced with permission

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Note 7 - Margin status (Required)


Complete resection of viable ‘malignant’ germ cell elements is an important prognostic factor in

RPLND and therefore is a required element. It is therefore important to liaise with the surgeon to

ensure that all margins are true margins, especially when adjacent lymph nodes/tissue is removed

individually. Use of marking sutures may be useful in these circumstances to indicate

orientation.17,18,24-26

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Note 8 - Extranodal extension (Required)


The detection of extranodal extension of disease has been studied in a number of publications, and

although some have shown it to be a poor prognostic indicator, this may not be independently

significant of other prognostic parameters such as tumour size, incomplete excision and type of

tumour. However, in the TNM staging it upstages from pN1 to pN2 and is utilised as a cut off point

for the decision on further chemotherapy.27,28

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8

Note 9 - Pathologic staging (Required)


This dataset includes the American Joint Committee on Cancer (AJCC) TNM 8th edition definitions.29

The implementation of AJCC TNM 8th edition has been deferred until January 2018 in some

jurisdictions. AJCC 7th edition30 and UICC 7th edition31 may be useful in the interim. Although

significant differences exist between the AJCC and UICC 8th editions for primary testicular tumours,

there are no such differences for pre or post treatment metastasis resections.

These required elements will depend on the nature of the resected specimens. Although most post-

chemotherapy resections are of lymph node groups, usually in the retroperitoneum, there are

occasional resections of other post-chemotherapy specimens from the lung, brain, liver or other

sites. Most, but not all of these specimens will either be of teratoma or show necrosis. All non-

lymphoid sites should be classified under M.

An alternative method of staging which may be used is the Royal Marsden method (see below),

which has been suggested in some studies to be more prognostically significant and helpful in

guiding further therapy than TNM and it is included below as it is requested by some oncological

centres.30-32

TNM8 Descriptors for RPLNDs and other metastatic resections of primary testicular neoplasms29

Regional lymph nodes (pN)

The regional lymph nodes are the abdominal para-aortic (peri-aortic), pre-aortic, interaortocaval

precaval, paracaval, retrocaval, and retro-aortic nodes. Nodes along the spermatic vein should be

considered regional.

Laterality does not affect the N classification.

The intrapelvic and the inguinal nodes are considered regional after scrotal or inguinal surgery.

pNx Regional lymph nodes cannot be assessed.

pN0 No regional lymph node metastasis.

pN1 Metastasis with a lymph node mass 2 cm or smaller in greatest dimension and less than or

equal to five nodes positive, none larger than 2 cm in greatest dimension.

pN2 Metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest

dimension; or more than five nodes positive, none larger than 5 cm; or evidence of

extranodal extension of tumour.

pN3 Metastasis with a lymph node mass larger than 5 cm in greatest dimension.

Distant metastasis (pM) (if resected)

No distant metastases

pM1 Distant metastasis.

pM1a Non-retroperitoneal nodal or pulmonary metastases.

pM1b Non-pulmonary visceral metastases.

A “y” prefix indicates those cases in which classification is performed during or following initial

9

multimodality therapy (i.e., chemotherapy, radiation therapy, or both chemotherapy and radiation

therapy).

Modified Royal Marsden Staging System

Stage I Tumour confined to the testis

Stage II Infradiaphragmatic nodal involvement

IIA greatest dimension of involved nodes less than 2 cm

IIB greatest dimension of involved nodes 2 cm or more but less than 5 cm

IIC greatest dimension of involved nodes 5 cm or more but less than 10 cm

IID greatest dimension of involved nodes 10 cm or more

Stage III Supraclavicular or mediastinal involvement

Stage IV Extranodal metastases

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Neoplasia of the Testis - Retroperitoneal …...Neoplasia of the Testis - Retroperitoneal Lymphadenectomy Histopathology Reporting Guide Not provided SIZE OF LARGEST NODAL METASTASIS